【作者】 卫毅；

【导师】 石翊飒； 马永丰；

【作者基本信息】 兰州大学 ， 麻醉学， 2009， 硕士

【摘要】 目的:观察N-甲基-D-天门冬氨酸(N-methyl-D-aspartate,NMDA)受体NR2B亚基反义寡核苷酸对吗啡依赖大鼠戒断症状和海马NMDA受体亚基mRNA表达的影响。方法:鞘内置管成功的成年雌性SD大鼠32只,随机分为4组(n=8):正常对照组(A组)、吗啡依赖组(B组)、反义药物组(C组)、正义药物组(D组)。B、C、D三组采用吗啡递增给药法制备大鼠慢性依赖模型,C组、D组在吗啡皮下注射的同时分别鞘内注射15nmol反义寡核苷酸或正义寡核苷酸。观察各组纳洛酮激发戒断症状评分、体重减轻数及海马NMDA受体NR1、NR2A和NR2B亚基mRNA表达的变化。结果:与B组相比,C组戒断症状的总评分和体重减轻数降低(P＜0.01);与A组相比,B组、D组海马NR2B亚基mRNA表达上调(P＜0.01);与B组相比,C组NR2B亚基mRNA表达下调(P＜0.01),C组NR2A亚基mRNA表达上调(P＜0.05);NR1亚基mRNA表达变化无统计学意义。结论:鞘内注射NR2B反义寡核苷酸可以有效抑制吗啡依赖大鼠戒断症状的形成,其机制与海马NMDA受体亚基数量和构成的变化调节有关。更多还原

【Abstract】 Objective :To investigate the influence of NR2B antisense oligonucleotide on the mRNA expression of N-methyl-D-aspartate receptor (NMDAR) subunits in the rat hippocampus and how this relates to morphine dependence.Methods :Thirty-two adult female Sprague-Dawley rats weighing 230～270g were randomly divided into 4 group(n=8 each): A control; B morphine dependence; C NR2B antisense oligonucleotide (ANR2B); D NR2B sense oligonucleotide (SNR2B). A model of chronic morphine dependence was established by repeated subcutaneous injection of morphine with progressive doses. Additionally, rats were treated with intrathecal (i.t.) injection of either saline, ANR2B or SNR2B. Morphine dependence was characterized by the total score of naloxone-precipitated withdrawal and weight loss .The method of reverse transcription polymerase chain reaction (RT-PCR) was used to study the expression of NR1, NR2A and NR2B mRNA in rat hippocampus.Results :The total score of morphine-withdrawal symptoms and the number of weight loss were higher in group B or D than in group C (P<0. 01). Increase in NR2B mRNA expression in the hippocampus induced by morphine were significantly attenuated by ANR2B.Conclusions :These results indicate that morphine dependence is related to the regulation of NMDA receptor ’ s level and construction in thehippocampus.更多还原